in Mental Health
Open Access
Case report
Sudden psychotic episode probably due to meningoencephalitis and
Chlamydia pneumoniae acute infection
Miguel Xavier*
1, Bernardo Correa
1, Marta Coromina
2, Nuno Canas
3and
João Guimarães
3Address: 1Depart. Psychiatry and Mental Health, Faculty Medical Sciences – UNL Calçada da Tapada, 155, 1300-Lisbon, Portugal, 2Depart. Psychiatry – Hospital S. Francisco Xavier, 1400-Lisbon, Portugal and 3Depart. Neurology, Hospital Egas Moniz, 1400-Lisbon, Portugal Email: Miguel Xavier* - xavierm@sapo.pt; Bernardo Correa - bernardocorrea@sapo.pt; Marta Coromina - marta.coromina@oninet.pt; Nuno Canas - nunocanas@netcabo.pt; João Guimarães - joaoguimaraes@hegasmoniz.min-saude.pt
* Corresponding author
Abstract
Background: Since 9% to 20% of all cases of acute psychosis presenting to an Emergency Department (ED) are due to a general medical condition, cautious medical workup should be mandatory in such patients. Differential diagnosis must consider conditions as diverse as renal failure or CNS infection.
Acute Chlamydia pneumoniae infection usually causes a self-limited respiratory syndrome. Rarely, acute neurological complications occur, with acute meningoencephalitis most frequently reported. Diagnosis requires a high level of suspicion and is difficult to confirm.
Case report: We describe a 22 year-old female Caucasian who, three days after a mild pharingitis, developed an acute psychosis with exuberant symptoms interspersed with periods of lucidity, in a background of normal consciousness and orientation.
Initial medical and imagiological workup were inconclusive. After 20 days of unsuccessful treatment with antipsychotics she developed a high fever and was re-evaluated medically. Lumbar puncture revealed an inflammatory cerebrospinal fluid. MRI showed irregular thickening and nodularity of the lateral ventricles' lining. An anti-Chlamydia pneumoniae IgM antibody titter of 85 IU/ml was detected. All symptoms cleared after treatment with antibiotics and corticosteroids.
Conclusion: This is, to our knowledge, the first reported case of acute CP-associated meningoencephalitis manifesting as an acute psychotic episode. It illustrates the principle that non-organic psychiatric syndromes must remain a diagnosis of exclusion in first-time acute psychosis.
Background
It is estimated that between 9% and 20% of all cases of acute psychosis presenting to an Emergency Department (ED) are due to a general medical condition [1-3]. This means that all patients coming to the ED with signs and symptoms of acute psychosis must undergo a careful
diag-nostic workup. Apart from non-organic psychiatric syn-dromes themselves, the differential diagnosis must include physical trauma, drugs and toxins, organ failure (e.g., renal failure), structural lesions like intracranial hematomas or neoplasms, infections and nutritional defi-ciencies like vitamin B12 deficiency or pellagra [1-4]. The
Published: 15 September 2005
Clinical Practice and Epidemiology in Mental Health 2005, 1:15 doi:10.1186/1745-0179-1-15
Received: 06 September 2005 Accepted: 15 September 2005
This article is available from: http://www.cpementalhealth.com/content/1/1/15
© 2005 Xavier et al; licensee BioMed Central Ltd.
psychiatrist plays a fundamental role in this process and is often the last resort that keeps the patient from sliding down the almost no-return path of an erroneous non-organic psychiatric diagnosis [2,4,5]. The sudden onset of psychosis in a 40 year-old patient with no personal or family history of psychiatric disease who shows recent memory loss, altered vital signs and a clouded conscious-ness with disorientation and visual hallucinations will probably be easily identified as a possible medical condi-tion manifesting through behavioural changes [5]. Many cases, however, do not present such clear-cut features and false beliefs (i.e. delusions) may actually constitute the sole manifestation of central nervous system disfunction (CNS) [6]. Such patients often come to constitute a true challenge to the attending psychiatrist.
Chlamydia pneumoniae (CP) is an intracellular organism with worldwide distribution and is pathogenic both to humans and other vertebrates. The metabolically inactive but infectious extracellular form (elementary body) differ-entiates into reticulate body after endocytosis by macro-phages/monocytes, endothelial cells or vascular smooth muscle cells. Within these cells it then replicates by binary fission [7]. It is currently speculated that the respiratory tract be the site of entry for CP, from whence it is then transported by monocytes or macrophages to other sites in the organism. It remains unclear how CP infection leads to disease, as it does not produce toxins and has only weak lipopolysaccharide activity [8]. In humans CP most frequently causes a self-limited and uneventful acute res-piratory tract syndrome. More rarely it can cause multior-ganic disease with an occasionally fatal outcome [8,7,9]. Over the last few years CP has become the object of intense debate among neurologists as being possibly involved in the aetiology of such diverse conditions as Alzheimer's disease, multiple sclerosis or atherosclerosis (this last possibility earning it the ironical nickname "car-diology's Helicobacter") [10-18]. Acute neurological com-plications of CP infection seem to be rare [10]; as to our knowledge no more than twenty putative cases with vari-able manifestations have been published so far [19-25]. Meningoencephalitis has been by far the most frequently reported situation, with isolated reports of meningo-radiculitis, polyradiculoencephalitis, cerebelar disfunc-tion, Guillain-Barré syndrome and acute disseminated encephalomyelitis. In most such cases direct evidence of central nervous system (CNS) involvement by CP in has been difficult to obtain; to our knowledge only three cases have been reported where intrathecal production of spe-cific anti-CP antibodies was demonstrated [19-21]. In a further case the authors claim to have detected CP anti-gens in their patient's CSF and more recently a case was reported where intrathecal presence of CP DNA was detected by PCR [23,25].
Case report
leuko-cyturia) and acyclovir. Five days levofloxacin was changed to gentamicin plus piperacillin/tazobactam for due to Escherichia coli-positive blood-cultures (serological results were not yet available at that time). She finally received three consecutive ev pulses of methylpred-nisolone (1 g each), before being transferred to a Neurol-ogy unit. During the following week she progressively became apyretic and her psychotic symptoms gradually remitted. At the time of discharge, eight weeks after admis-sion, she still had an ESR of 55 mm/h and a CRP of 9.03 mg/L, with normal blood count and biochemical param-eters as well as a normal CSF. Brain MRI nine weeks after admission showed complete remission of the initial changes. At the time of discharge, the EEG still displayed symmetrical, irregular, high amplitude, slow wave activity with frontotemporal predominance, although much less severe than in the first EEG record.
Psychiatrically she remained slightly disinhibited, both verbally and affectively, with pedolalia and mildly child-ish behaviour. There were no signs of delusional ideas or hallucinations and she could only vaguely remember the period when she had been psychotic. Two months after discharge she had resumed her studies and concluded her Business School degree.
Discussion
This is, to our knowledge, the first reported case of an acute CP-associated meningoencephalitis manifesting as a first-episode acute psychosis.
In our patient the initial manifestations were interpreted as a purely non-organic psychiatric syndrome, which led to a delay of several weeks not only in the definitive diag-nosis but also in the appropriate treatment. The patient's young age, her clear consciousness and normal orienta-tion, the presence of archetypical first-rank symptoms of schizophrenia and specially her normal physical and neu-rological examinations were all factors contributing to the premature exclusion of a medical condition as an explana-tion for the patient's behavioural changes. This illustrates how easy it can be to miss an organic brain syndrome at an early stage once a psychiatric diagnosis is taken into consideration and in the absence of such gross indicators as age greater than 40 years, disorientation with clouded consciousness or abnormal vital signs. Retrospectively we can identify several subtle cues in our patient pointing to a medical aetiology, namely the sudden onset of severe and exuberant psychiatric changes, the patient's high level of functioning prior to the episode and negative family history for psychiatric disorders, her intense emotional unsteadiness, the temporal relationship to a minor infec-tious episode, the existence of occasional "islands" of lucidity and the symptoms' minimal response to antipsy-chotic agents. All of these have been consistently reported
in the literature as discrete but highly significant indica-tors of acute organic brain disorder [1,2,4,5,26,27]. A pertinent question in this context is which diagnostic methods should be included in the initial workup of first-episode acute psychosis. Although most would probably include a no-contrast brain CT scan in their initial evalua-tion, this is actually a method lacking in sensitivity [1-3,27]. On the other hand, MRI scanning is probably una-vailable in most EDs. Also, the decision threshold for per-forming a lumbar puncture should be much lower, since it remains the most reliable method of detecting inflam-matory changes of the CNS [1,3].
Our case is also worthy of discussion from the perspective of infectiology, especially insofar as the final bacteriolog-ical diagnosis is concerned. CP infection of the CNS is dif-ficult to diagnose and requires a high level of suspicion. Detection of the organism's DNA in the CSF using polymerase chain reaction (PCR) probably constitutes the most reliable method of confirming the diagnosis [25,28,29]. Unfortunately, this is a method that is not always available, as it is the case in our hospital. However, the elevated titer of CP IgM antibodies in the serum and the absence of any other possible aetiology after exhaus-tive investigation make CP the almost certain cause of meningoencephalitis in our patient. To our knowledge only three cases where intrathecal synthesis of CP anti-bodies was demonstrated have been published so far and most reports of the rare acute neurological complications of CP infection have been based on serum antibody titers only [19-21]. Moreover, Sočan et al, using a direct-immunfluorescence test with CP-specific monoclonal antibodies, reported a case where they detected CP gens in their patient's CSF, which showed negative anti-body titers by microimmunofluorescence assay [23].
microimmun-ofluorescence assays for measuring antibody titers in the serum, while our patient was studied using an enzyme-linked imunosorbent assay. The whole controversy around which is the most reliable method for detecting CP infection of the CNS actually developed in connection with attempts to link the organism to the aetiology of Multiple sclerosis, Alzheimer's disease or atherosclerosis, leading to the active search for CP in patients with no other evidence of infection by CP than the above-men-tioned conditions themselves [11-13,15-17,30]. To be conclusive, this kind of investigation must strive for a degree of certainty and unambiguity in their methods whose sophistication and complexity are probably inade-quate for everyday use in a clinical context.
Another important question in our case is what caused the patient to improve. The fact that she only received levo-floxacin for five days (serological results were only availa-ble after the patient had started to improve) and her rapid recovery after corticosteroid therapy suggests that the acute neurological complications of CP infection might be attributed to an autoimmune mechanism, rather than to the organism's direct action. Frydén et al have previ-ously reported improvement after corticosteroid therapy in CP-associated meningoencephalitis (although their patient also received cloramphenicol) [31]. The CP-asso-ciated Guillain-Barré syndrome reported by Haidl also recovered only after treatment with methylprednisolone [24]. The encephalitis case reported by Airas et al suffered further clinical and imagiological progression in spite of CP-active antibiotic treatment (levofloxacin) [19]. The case reported by Michel et al eventually recovered from lumbosacral meningoradiculitis without antibiotic treat-ment [21]. Finally, Grayston et al described a case where acute CP reinfection led to a sarcoidosis-like clinical pic-ture and raise the possibility of an immunopathologic reaction in their patient [9].
In spite of our current ability to detect structural and func-tional changes of the CNS in organic brain syndromes, it remains unclear how these changes relate to the behav-ioural changes and in what way such observations might be extrapolated to our understanding of the pathophysiol-ogy of non-organic psychosis. In the present case the only observable changes seemed to concentrate around the ependymal axis. Peri-aqueductal structures have recently been considered by a few authors to be the neurostruc-tural backbone of consciousness and especially of the con-sciousness of the self, whose disturbance constitutes one of essential features of schizophrenic psychosis [32,33]. This concept is in full accordance to the observations by Cummings et al, who found that in organic psychosis complex symptomatology such as Schneiderian first-rank symptoms is more frequently associated with subcortical lesions. This probably means that complex psychotic
syn-dromes require that higher CNS functions like linguistic and verbally-mediated conceptual abilities and the corre-sponding cortical structures be intact. Subcortically gener-ated abnormal emotional experiences can thus be fully elaborated at higher levels into complex delusional and hallucinatory syndromes [6]. Interestingly, organic psy-chosis due to subcortical brain lesions also seem to be par-ticularly resistant to antipsychotic treatment, which was one of the striking features of our patient [6].
Conclusion
As we stressed before, this is to our best knowledge the first reported case of an acute CP-associated meningoen-cephalitis manifesting as a first-episode acute psychosis and illustrates the overwhelming importance of a careful medical and neurological diagnostic workup before a sud-den first-time psychotic episode receives a "non-organic" psychiatric diagnosis. In such cases non-organic psychiat-ric diagnosis should remain a diagnosis of exclusion [1,4], and thus approached with the assumption that the cause of psychosis is an organic one [4]. As diagnostic methods grow more complex and as we become more able to diag-nose unusual medical aetiologies for common psychiatric syndromes, more and more will be demanded from clini-cal psychiatrists in terms of general mediclini-cal knowledge and ability to work fully integrated with other specialities.
Competing interests
The author(s) declare that they have no competing inter-ests.
Authors' contributions
MX wrote and submitted the manuscript
BC helped to draft the manuscript and reviewed pub-lished references
MC and NC have made substantial contributions to acquisition and interpretation of clinical data:
JG revised the manuscript critically from the neurological point of view
All authors read and approved the final manuscript. More-over, all authors were involved in the care of the patient described in this case report
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